Genentech zeroes in on targets beyond cancer

Cancer-fighting drugs remain king at Genentech Inc., but a new crop of experimental therapeutics is thrusting the biotech pioneer into Alzheimer’s disease, schizophrenia, multiple sclerosis and infectious diseases like cytomegalovirus.

By far, the South San Francisco-based U.S. beachhead for Swiss drugmaker Roche continues to be a powerhouse of anti-cancer drug research. Genentech and its collaborators are running some 40 cancer medicines through more than 600 studies. What’s more, its new-wave cancer drugs are targeting combinations and new technologies that make therapies safer, more powerful and precise.

But Genentech clearly is stepping out in new directions, with more than a dozen neuroscience projects in various stages, said Lori Martin, vice president of new products commercialization in neuroscience and cardiometabolism.

The company made its first appearance at the recent American Psychiatric Association meeting in San Francisco, for example.

“The objective is to introduce Genentech to the psychiatric community and bring home that we are committed to the science and patients, and that we will bring that same commitment and focus that we’re known for in oncology,” Martin said.

And Genentech has something concrete to show doctors as well, the schizophrenia drug bitopertin. The drug — designed to treat so-called “negative symptoms” of schizophrenia like social withdrawal and apathy, as opposed to “positive symptoms” like delusions and hallucinations — is in six Phase III trials.

Those trials start reporting data in the first part of next year, Martin said, and could lead it to ask the Food and Drug Administration in early 2015 to approve bitopertin.

Other Genentech neuroscience projects revolve around Alzheimer’s disease, obsessive-compulsive disorder, major depressive disorder, autism and multiple sclerosis. Those are areas where new drug approvals have been few and far between.

“We’ve been looking into the sciences of these diseases for a while,” Martin said. “We see signals of how to follow the biology and we’re committed to meet that in these areas of unmet need.”

No matter how successful, though, the new drugs will not bump Genentech’s multibillion-dollar-a-year cancer franchise. Solidifying cancer’s lead at the company, Genentech won FDA approval in February of Kadcyla, or T-DM1, and Perjeta won FDA approval in June 2012 against breast cancer.

Kadcyla is one of 25 so-called antibody-drug conjugates in Genentech’s pipeline of cancer drugs.

Many of those drugs use bedrocks of Genentech’s cancer franchise, such as Avastin and Herceptin. In fact, $9,800-per-month Kadcyla couples Herceptin with a chemotherapy agent developed by ImmunoGen Inc. of Waltham, Mass., to find a more precise landing pad on a cancer cell and delink its toxic payload inside the cell.

Genentech is testing a combination of Perjeta and Kadcyla. Results of that trial could be available by the end of 2013.

“What’s important here is to do the right thing for patients,” said Philippe Bishop, Genentech’s vice president of clinical development and global head of its cancer angiogenesis franchise.

At the recent American Society for Clinical Oncology meeting in Chicago, Genentech unveiled more Phase III data around GA-101, its drug against the blood cancer chronic lymphocytic leukemia, as well as data from six early-stage studies of anti-PDL1, a drug that triggers the body’s own immune system to mount an attack on cancer cells.

GA-101 is a next-generation drug that could replace Rituxan, the first monoclonal antibody approved for therapeutic use. Rituxan, which was discovered by Biogen Idec and co-marketed in the United States by Biogen and Genentech, loses its patent protection in 2018, and Genentech sees the combination of GA-101 and the chemotherapy agent chlorambucil as a more effective and better-tolerated alternative.

“We have the opportunity to take molecules in early development and combine them,” said Dr. Nancy Valente, global head of Genentech’s hematology franchise. “It is especially gratifying and possible at Genentech because of the depth and breadth of our pipeline.”

In the pipeline

Here is a taste of what Genentech is working on:

MPDL-3280A

Target: Various cancer types

Immunotherapy, or summoning the body’s own immune system army to mount an attack on cancer, is an important Genentech campaign, and the company’s anti-PDL1 therapy, dubbed the unsexy experimental name MPDL-3280A, is a frontline soldier.

Doctors have been excited by the potential of cancer immunotherapy for years, but clinical results have been up and down. Recently, the pendulum swung back.

Genentech’s therapy makes cancer cells more vulnerable to immune system attacks by disrupting a protein called PD-L1. A Phase I study of 275 patients showed early safety and efficacy signals.

GA-101

Target: Chronic lymphocytic leukemia

The drug is built to change the sugar molecules in the drug, and Genentech scientists believe that makes a difference in how immune cells attack and eliminate tumor cells in patients with chronic lymphocytic leukemia.

CLL patients today are treated with a variety of agents, including the Genentech-Biogen Idec drug Rituxan in combination with chemotherapy. But some aggressive regimens are too toxic for CLL patients, whose mean age is 72, said Dr. Nancy Valente, global head of Genentech’s hematology franchise.

Enter GA-101 — the first glycoengineered antibody in trials — which studies have shown is well tolerated and effective.

Crenezumab and an anti-tau antibody

Target: Alzheimer’s disease

Genentech is working with Swiss biotech AC Immune SA on crenezumab, an antibody that targets the presumed cause of plaques in the brain, and a preclinical antibody that zeros in on a protein called tau.

Crenezumab, designed to bind to amyloid beta, or Abeta, which forms plaques in the brain, is the center of a first-ever Alzheimer’s prevention study in Colombia in cognitively healthy people who are likely to develop Alzheimer’s due to their genetic history.

Tau is a relatively new target in Alzheimer’s, implicated in the spread of the disease. The protein tends to accumulate and tangle inside the neurons of Alzheimer’s patients.

Bitopertin

Target: Negative symptoms of schizophrenia

While schizophrenia patients can be treated with drugs for so-called “positive symptoms,” such as delusions, there is no treatment for “negative symptoms” like the social withdrawal that tends to precede a formal diagnosis.

Genentech expects to file for FDA approval of bitopertin in early 2015, Martin said. It would be Genentech’s first neuroscience drug approval.

Bitopertin, an oral small molecule, works by helping regulate the amount of glycine, an amino acid neurotransmitter that is essential for a key receptor, called NMDA.